Document Detail

Novel Cinnamyl Hydroxyamides and 2-Aminoanilides as Histone Deacetylase Inhibitors: Apoptotic Induction and Cytodifferentiation Activity.
MedLine Citation:
PMID:  21374822     Owner:  NLM     Status:  Publisher    
Four novel series of cinnamyl-containing histone deacetylase (HDAC) inhibitors 1-4 are described, containing hydroxamate (1 and 3) or 2-aminoanilide (2 and 4) derivatives. When screened against class I (maize HD1-B and human HDAC1) and class II (maize HD1-A and human HDAC4) HDACs, most hydroxamates and 2-aminoanilides displayed potent and selective inhibition toward class I enzymes. Immunoblotting analyses performed in U937 leukemia cells generally revealed high acetyl-H3 and low acetyl-α-tubulin levels. Exceptions are compounds 3 f-i, 3 m-o, and 4 k, which showed higher tubulin acetylation than SAHA. In U937 cells, cell-cycle blockade in either the G(2) /M or G(1) /S phase was observed with 1-4. Five hydroxamates (compounds 1 h-l) effected a two- to greater than threefold greater percent apoptosis than SAHA, and in the CD11c cytodifferentiation test some 2-aminoanilides belonging to both series 2 and 4 were more active than MS-275. The highest-scoring derivatives in terms of apoptosis (1 k, 1 l) or cytodifferentiation (2 c, 4 n) also showed antiproliferative activity in U937 cells, thus representing valuable tools for study in other cancer contexts.
Sergio Valente; Maria Tardugno; Mariarosaria Conte; Roberto Cirilli; Andrea Perrone; Rino Ragno; Silvia Simeoni; Anna Tramontano; Silvio Massa; Angela Nebbioso; Marco Miceli; Gianluigi Franci; Gerald Brosch; Lucia Altucci; Antonello Mai
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-4
Journal Detail:
Title:  ChemMedChem     Volume:  -     ISSN:  1860-7187     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101259013     Medline TA:  ChemMedChem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza", P.le A. Moro 5, 00185 Roma (Italy), Fax: (+39) 06-49693268.
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